1065 - Early tumour shrinkage (ETS), depth of response (DpR) and associated survival outcomes in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC) classified according to Köhne prognostic category: retrospective analysis of the panitumumab (Pmab) PRIME study

Background

Köhne prognostic category classifies mCRC pts as high, medium or low risk. Retrospective analysis of phase 3 trials found that Köhne category predicts survival, pts with BRAF mutant (MT) mCRC represent a separate (higher risk) category, and Pmab-based therapy improves survival vs chemotherapy alone in all four risk groups. We evaluated whether higher Köhne category and BRAF status predicts worse ETS and DpR, and assessed outcomes by ETS ≥30% vs < 30% and DpR category.

Methods

Retrospective analysis of RAS WT mCRC pts from the phase 3 PRIME study. ETS (% reduction in the sum of the longest diameters of measurable lesions at week 8) and DpR (maximum % change from baseline to nadir [shrinkage]; % change at progressive disease [no shrinkage]) were analysed according to Köhne category. DpR groups: <0%; 0–30%; 31–52%; 53–70%; 71–100%. BRAF MT pts were considered separately. Treatment arms were pooled and analysed separately.

Results

436 pts receiving treatment (FOLFOX±Pmab) were analysed for ETS, 456 for DpR. The % pts in low-, medium-, high-risk and BRAF MT groups, respectively, achieving ETS ≥30% was 63.8%, 50.4%, 41.9% and 21.7%, and DpR 71–100% was 47.7%, 23.6%, 10.0% and 4.2%. Pts with ETS ≥30% vs < 30% achieved longer PFS and OS, irrespective of Köhne category; this effect was not seen in BRAF MT pts (Table). In all Köhne groups, deeper DpR was generally associated with longer PFS and OS; this trend was noted in the BRAF MT group, but to a lesser extent. For all analyses, similar trends were seen in individual treatment arms (data not shown).Table:

572P Median PFS and OS by ETS ≥30% vs < 30% and by DpR category for each Köhne prognostic category and in pts with BRAF MT mCRC. P+F=Pmab+FOLFOX, F=FOLFOX alone

Number of patients evaluable for ETS and DpR differ as patients with disease progression or death before week 8 did not have ETS data available;.

For ETS ≥30%: n = 128 (P+F), n = 83 (F); ETS <30%: n = 88 (P+F), n = 137 (F);.

For DpR <0%: n = 17 (P+F), n = 26 (F); 0–30%: n = 42 (P+F), n = 47 (F); 31–52%: n = 52 (P+F), n = 54 (F); 53–70%: n = 57 (P+F), n = 53 (F); 71–100%: n = 65 (P+F), n = 43 (F).

Conclusions

Higher-risk categories predict worse ETS and DpR in pts with RAS WT mCRC. Irrespective of risk category, pts achieving ETS ≥30% vs < 30% survived longer. Although patient numbers were small, prognosis in BRAF MT group was poor irrespective of ETS, but OS/PFS were longer with deeper DpR.

Clinical trial identification

NCT00364013.

Editorial acknowledgement

David Cutler, PhD, CMPP of Aspire Scientific (Bollington, UK) and funded by Amgen (Europe) GmbH (Rotkreuz, Switzerland).

Legal entity responsible for the study

Amgen (Europe) GmbH.

Funding

Amgen (Europe) GmbH.

Disclosure

A. Sartore-Bianchi: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Sanofi. M. Peeters: Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Amgen; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Roche; Honoraria (self): Lilly; Honoraria (self): Merck Serono; Honoraria (self): Remedus; Honoraria (self): Sanofi-Aventis; Honoraria (self): Servier; Honoraria (self): Sirtex; Honoraria (self): Terumo. M. Geissler: Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Sanofi. J. Taieb: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Sirtex. P. García-Alfonso: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Servier. T. Price: Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Roche. P. Burdon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen (Europe) GmbH. Y. Zhang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen Inc. C. Koehne: Honoraria (self): Amgen; Honoraria (self): Bayer; Honoraria (self): Merck; Honoraria (self): Pfizer; Honoraria (self): Servier.